For measuring parameters of a blood sample, such as blood gases, electrolytes and metabolites, an accurate control of the temperature of the sample to be examined may be required. Samples may be supplied into a conventional measurement apparatus at different temperatures, such as for example between 4° C. and 41° C. The measurement of the blood parameters is however required to be performed at a fixed temperature, such as for example 37° C. Such a temperature may for example be required to measure a partial pressure of oxygen, a partial pressure of carbon dioxide, to measure a pH or to measure an electrolyte concentration, such as calcium, sodium, potassium or chloride ions.
It may take some time to adjust the temperature of the sample to the intended measurement temperature. Furthermore, a measurement time is influenced by the time required to supply the sample into the measurement cell in the measurement apparatus. Further, the measurement time may be dependent on maximally possible pump velocities.
Furthermore, a measurement accuracy may depend on a possible change of the sample on the way from the external sample source to the measurement sensors due to carry-over effects (i.e. dilution). Also a possible entrapment of air bubbles may result in wrong measurements. The carry-over effects as well as the entrapment of air bubbles may most likely happen on positions where the material of the sample path changes. Different materials (e.g. steel, plastic, rubber, material of the sensor (casing) etc.) with which the sample may be in contact during supply to the measurement apparatus or during measurement itself may therefore influence the result of the measurement and thus may influence the measurement accuracy.
The required accuracy of the temperature regulation or temperature control may for example be 37° C.+/−0.2° C. Such accuracy of the temperature regulation may be required due to the temperature dependency of the solubility of gases within blood and within aqueous solutions, as well as the temperature dependency of the pH value for example. It may further be desired to use as little amount of sample as possible, while maintaining measurement accuracy. In this respect, the wetting properties of different materials of the measurement cell as well as the sample supply path may be relevant and also the constructional design of the measurement cell.
In conventional measurement systems, the sample may be heated along a pre-heating path which is integrated within the measurement apparatus. Other arrangements or concepts of the prior art directly heat up the sample within the measurement chamber by positioning the measurement cell or measurement chamber on or between temperature controlled heating blocks. Other systems of the prior art use measurement cells with sensor substrates having printed thereon resistance traces and a printed temperature sensor for changing and controlling the temperature of the sample, the measurement cell directly attached to the measurement apparatus in a fixed position.
EP 1 674 866 A1 discloses an arrangement for controlling the temperature of a measurement cell, wherein the measurement cell comprises a measurement channel in which a sensor element is arranged and an analyzer having a surface that can be temperature-controlled. The measurement cell can exchangeably be inserted into the analyzer and may be brought in contact with the surface which may be temperature-controllable. A heat conducting elastic or plastic layer is attached on a measurement cell wall or the surface which may be temperature-controllable.
EP 2 199 792 A1 discloses a method for examining the quality of a thermal coupling of a measurement cell, wherein the measurement cell is exchangeably insertable into an analyzer and comprises at least one sensor element within a measurement channel. The measurement channel is filled with a calibration liquid and a rapid temperature change is applied on the element which may be temperature-controllable and with which the measurement cell is in mechanical contact. Further, a time course of a signal of the at least one sensor element is acquired and the quality of the thermal coupling is determined based on an analysis of the time course of the signal.
U.S. Pat. No. 5,342,498 discloses an improved electronic wiring board having a thermistor and at least one blood gas sensor supported, in close relation, one to the other, on one side of the board and a heater supported on the other side of the board to provide heat in response to temperature sensed by the thermistor, to at least the region where the thermistor and the blood gas sensor are positioned on the board to control the temperature of the region of the board within a narrow distribution of temperatures.
U.S. Pat. No. 5,916,425 discloses an electronic wiring-substrate for sensors formed over a subminiature through-hole, wherein only a small amount of conductive material which fills each through-hole is in contact with each associated electrode. A relatively large number of sensors can be formed on the surface of the substrate within a relatively small fluid flow cell. This document also discloses a heater which is disposed within the substrate and which is capable of heating a blood sample and the array of sensors to a known stable temperature and maintaining that temperature as the sample is being analyzed, and a thermistor located in the sample path on the front side of the substrate. A number of sensors and independently controllable heaters (each one controlled by a thermistor) may be used to regulate the temperature of each sensor and the local temperature of the analyte at different locations along the flow path. The heater covers at least the area of the sample path.
A problem with the conventional systems and methods with a single heater in or on the sensor substrate is that the required temperature of the sample is not achievable in all situations in an acceptable time. In particular, when samples, for example blood, plasma, serum, have different temperatures, for example between 4° C. and 41° C., tempering the sample to a target temperature (for example 37° C.) and maintaining them at this temperature may not in all situations be possible in an acceptable time.
Other measurement systems and methods of the prior art have the disadvantage that a temperature controlled heating block and/or a pre-tempering path and/or a heated measurement chamber are used, to satisfy the requirements of the temperature control during the measurement. The heating block or the pre-tempering path are, due to cost issues, to be arranged within the measurement apparatus and cannot be placed into a consumable. Further, the thermal coupling between the heating block and the actual measurement cell is unknown and needs to be examined. The quality of the thermal coupling strongly influences the velocity or speed of arriving at a temperature of the sample that is required for the measurement.
Typical times to heat the sample to the desired target temperature conventionally are around 10 to 15 s. Using a pre-heating path may allow to reduce the time for achieving the desired target temperature, however, longer tubing is required Those skilled in the art know that this requires a higher sample volume due to carry-over effects and extends the time for the sample to be supplied to the measurement cell.
Another measurement system and method of the prior art has the disadvantage that a measurement cell with a heated sensor substrate is to be placed in a fixed position at the analyzer. This arrangement requires extended tubing paths, resulting in a higher sample volume, a higher demand of calibration liquids and a higher time effort for supplying these liquids.
In prior art solutions, the position of the measurement cell is fixed within or on the measurement apparatus. The supply of the sample thus necessarily is performed using extended tubing possibly resulting in a change/modification of the sample within the supply tubing. Further, the required minimal sample volume may be negatively affected. Due to the extensive tubing paths, also the minimally achievable measurement times are limited by a lower limit (for example 35 s) thereby lowering throughput.
There may be a need for a, in particular, movable measurement cell for measuring at least one constituent of a liquid sample, for a measurement system for measuring at least one constituent of a liquid sample, for a method for manufacturing a measurement cell and for a method for measuring at least one constituent of a liquid sample, wherein at least one of the above-mentioned disadvantages of the prior art are attenuated, reduced or even avoided.
In particular, it may be desired to provide a measurement cell that allows accurate and fast tempering of a sample and which at the same time enables accurate measurements on the sample, in order to measure at least one constituent. The measurement cell should be cheap to be placed in a consumable and should be independent of any other external heating devices to be placed in a position which allows the minimal possible sample path length.
The need may be satisfied by the subject-matter of the independent claims. The dependent claims specify particular embodiments of the present invention.